Intra tumoral Oxygenation; A Predictor for Treatment outcome in Cervical Cancer.

Radiotherapy is the mainstay of treatment for locally advanced (FIGO stage II *
IV) or bulky FIGO stage IB tumors and for medically inoperable patients.
In recent years, several randomized prospective trials have shown that
combination treatment with chemotherapy (chemoradiation) or with regional
hyperthermia (thermoradiation) has greatly improved tumor control and survival
Combined modality treatment is now regarded as the standard treatment for
locally advanced cervical cancer. Hypoxia and anaemia are considered some of
the key contributors to radioresistance and final outcome of initiated cancer
therapy. It is well known that hypoxia induces radioresistance. Results from a
recently published small-scale study indicate hyperthermia to effect both tumor
oxygenation as well as treatment outcome.
Invasive measurement of the partial pressure of oxygen by polarography using
the Eppendorf needle electrode is the most frequently applied method. It is
still considered as the *gold standard* for measurements of tissue PO2.

To study tumor oxygenation in woman with cervical carcinoma

Primarily: To study the feasibility of measuring tissue pO2 with the FDA
approved Eppendorf needle electrode and to correlate these results with
promising new non-invasive methods to measure hypoxia, using dynamic contrast
enhancement MRI and functional Blood Oxygenation Level Dependent MRI.
Eventually: We want to start a larger study with a more specific patient
population that receives combined modality treatment to assess the effect of
additional hyperthermia on:
* tumor hypoxia.
Specifically to determine the relationship between:
* tumor hypoxia measured by Eppendorf polarographic electrode system,
* tumor hypoxia measured with non-invasive techniques,
* expression of a selection of (potential) endogenous hypoxia markers and
cytokines in blood plasma.
and to correlate that relationship with:
* thermal dose,
* response to given therapy,
* local control,
* development of distant metastases,
* development of normal tissue toxicity,
in order to develop a non-invasive, prognostic method that is uniformly
applicable and will help to identify patients with poor prognosis who will
benefit most from additional hyperthermia treatment. In addition, optimization
of combined modality treatments involving hyperthermia might be accomplished by
adjusting temperature and treatment sequence in relation to oxygenation status
of the tumor to improve treatment response.

Pilot-study.
After given informed consent, tumor oxygenation will be measured in 10 patients
with cervix cancer, using a minimally invasive polarographic needle electrode
(Eppendorf pO2 histograph, Eppendorf, Hamburg, Germany). The first oxygenation
measurement will take place during the routine examination under anesthesia.
The second Eppendorf measurement will be done in week one of radiotherapy. If
patients receive hyperthermia treatment the second oxygenation assessment will
take place 24 hours after the first hyperthermia treatment. A non-invasive
method of tumor hypoxia measurement will be used with the methodology of
dynamic contrast enhanced MRI and BOLD fMRI, before treatment, immediately
after the diagnostic scan. During routine blood analysis extra blood samples
(10 ml) are taken on a weekly basis for a period of 6 weeks.

Extra MRI-scan will be performed
During routine examination under anesthesia a tumor oxygenation assessment will
take place, but this procedure is asociated with a minimal risk of bleeding or
pain.
The second oxygenation measurement requires an addiotional vaginal examination
During routine blood analysis extra blood samples (10 ml) are taken on a weekly
basis for a period of 6 weeks.